title: Molecular characterization of isoniazid-resistant Mycobacterium tuberculosis isolates from Xi'an, China.
abstract: The increased prevalence of isoniazid (INH)-resistant tuberculosis (TB) has become a significant challenge for TB control in the last 10 years. It has been reported that INH resistance is most frequently associated with katG 315 and inhA-15 mutations. The relative significance of these mutations in INH-resistant Mycobacterium tuberculosis and their association with the different genotypes of M. tuberculosis in Xi'an, China, was investigated. Eighty-nine INH-resistant isolates were subjected to molecular characterization of hotspot mutations within katG 315 and inhA-15 by Multiplex allele-specific PCR, and results from 10 isolates were confirmed by direct sequencing. Mutations in katG 315 and inhA-15 were detected in 58 and 7 isolates, respectively. These isolates were genotyped by mycobacterial interspersed repetitive unit-variable number of tandem repeats and Spoligotyping. Spoligotyping showed that 79 isolates (89%) belonged to Beijing family. Mycobacterial interspersed repetitive unit-variable number of tandem repeats typing revealed significant differences in clustering level between Beijing and non-Beijing family (56% vs. 9%, p = 0.002), which indicated the active transmission of Beijing family in INH-resistant isolates. Our results suggested that the katG 315 mutants were predominant in INH-resistant isolates in Xi'an and the hotspot mutations within katG 315 and inhA-15 can be used as genetic markers for detection of INH resistance.
authors.affiliation: Department of Medical Microbiology and Parasitology, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Aiping
authors.initials: A
authors.lastname: Zhou
authors.forename: Muhammad
authors.initials: M
authors.lastname: Nawaz
authors.forename: Yan
authors.initials: Y
authors.lastname: Duan
authors.forename: John E
authors.initials: JE
authors.lastname: Moore
authors.forename: Beverley Cherie
authors.initials: BC
authors.lastname: Millar
authors.forename: Jiru
authors.initials: J
authors.lastname: Xu
authors.forename: Yufeng
authors.initials: Y
authors.lastname: Yao
mesh_terms: D000483:Alleles; D000995:Antitubercular Agents / Q000494:pharmacology; D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism; D015373:Bacterial Typing Techniques; D002374:Catalase / Q000235:genetics* / Q000378:metabolism; D002681:China; D004269:DNA, Bacterial / Q000032:analysis; D024881:Drug Resistance, Bacterial / Q000187:drug effects / Q000235:genetics*; D005798:Genes, Bacterial; D005819:Genetic Markers; D005838:Genotype; D006801:Humans; D007538:Isoniazid / Q000494:pharmacology*; D008168:Lung / Q000382:microbiology* / Q000473:pathology; D008826:Microbial Sensitivity Tests; D017720:Molecular Epidemiology; D009154:Mutation; D009169:Mycobacterium tuberculosis / Q000145:classification / Q000187:drug effects* / Q000235:genetics* / Q000302:isolation & purification; D010088:Oxidoreductases / Q000235:genetics* / Q000378:metabolism; D010802:Phylogeny; D016133:Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D020080:Tandem Repeat Sequences; D018088:Tuberculosis, Multidrug-Resistant / Q000188:drug therapy / Q000453:epidemiology / Q000382:microbiology* / Q000635:transmission
chemical_list: D000995:Antitubercular Agents; D001426:Bacterial Proteins; D004269:DNA, Bacterial; D005819:Genetic Markers; D010088:Oxidoreductases; D002374:Catalase; C480353:katG protein, Mycobacterium tuberculosis; C085257:InhA protein, Mycobacterium; D007538:Isoniazid